The "goal" of most infectious agents is to maintain their existence by replicating and to propagate by spreading within ecological niches, such as an animal population. Many are have evolved sophisticated mechanisms to survive in all aspects of transmission between infected and susceptible animal hosts, much understanding of which is relatively recent. Many infectious agents are often in intense competition with other flora, such as in the host intestinal tract, and have evolved mechanisms enabling them to survive this competition. Infectious agents are also well equipped to adapt to new ecological niches, such as those presented by changing husbandry practices (e.g. use of recycled flush water for manure removal on dairies) or the movement of animals into new environments (e.g., llamas and alpacas from South American highlands to temperate low lands).

Many of infectious agents co-evolved with their animal hosts and were perpetuating successfully long before man imposed domestication on these hosts. Domestication has upset the "natural" medical ecology under which this co-evolution occurred and thus has changed the natural history of many infections. Man's changing husbandry and management factors continue to do so. For example, higher animal stocking densities increase effective contacts for many agents, particularly those transmitted by direct contact.

Why does this matter?

Many infectious agents have several mechanisms to exchange genetic material with unrelated species and to change the genetics of their progeny, have very short generation times compared to livestock and are rapidly and constantly changing as a result. While we deliberately select domestic animals, we also unwittingly select their infectious agents. We steadily apply selection pressure in the form of antibiotics, transportation, and new housing and feeding systems. Antibiotic usage selects those infectious agents that the antibiotics don’t work against. Animal management systems select those infectious agents that are able to survive and proliferate in them

In one Holstein selection cycle (2 years), bacteria have 175 times as many opportunities for change as has occurred in over 100 years of dairy breeding. Given the dramatic milk yield increase that has occurred with 50 years of intense selection, where will the Holstein be after 17,500 years?  That is equivalent to the opportunity that bacteria have for change every two years under optimal growth conditions.

Usually the goal of the clinician is to prevent clinical disease from ubiquitous agents (agents most likely already infecting a herd) and to eradicate non-ubiquitous agents from infected herds or to prevent their entry into non-affected herds. For the major infectious, communicable diseases in their species of interest, to accomplish these goals the clinician needs to understand the medical ecology and natural history of the disease sufficiently to:

• Prevent an animal or a group of animals from acquiring it (primary prevention).
• Control or eliminate such an infection in a group of animals once it is present (secondary prevention).

The following is a basic framework of questions for organizing this information:

• What is the reservoir(s) of the agent? What is the potential for susceptible animals to be exposed to this reservoir (Shedding level or environmental level vs. chance of contact or infectious dose)? What conditions favor spread from the reservoir? Which inhibit it?
• What is the typical period of communicability? What is the typical shedding pattern and level over this period? The longest period? What proportion of infected animals become chronic or latent carriers?
• How can subclinical carriers be detected? Incubating or latent carriers?
• What is the diagnostic performance of each of the available tests across the spectrum of infection and the stages (incubation, florid disease, convalescence) in the natural history of the disease?
• For an infectious agent, what is the typical level of shedding (e.g., colony forming units (CFU) per gram of discharge) by clinical and by subclinical cases?
• What is the primary mode of transmission? Secondary modes? What are the relative importance's of these?
• If a mechanical or biological vector is involved, what factors influence its survival and transmitting ability? How can contact between the vector and susceptible animals be reduced or prevented? How long can mechanical vectors present a risk to susceptible animals?
• What are the environmental survival characteristics of the agent?

Is it significantly affected by freezing? By desiccation? By sunlight (UV)? How long does it typically survive at infectious levels in associated biological materials (e.g. feces, urine, saliva, nasal discharge, and cadavers)? In soil? In water? On surfaces?

What practical sanitation procedures will eliminate it?

• What is the minimum dose that will typically cause infection (infectious dose)? Clinical disease? How does this compare to the typical level of exposure?

What are the shedding levels of subclinically infected animals compared to clinically infected animals? How dangerous to susceptible animals are subclinically infected animals? Clinically infected animals?

• What host factors increase susceptibility? Resistance?
• What is the typical incubation period? What is its range (shortest to longest)?
• In a typical group of animals with the infection present, what are the proportions of subclinically and clinically infected animals during a clinical outbreak? During an endemic phase?
• What vaccines are available? 

  What is the efficacy of vaccination? How do the different types of vaccination affect the development of clinical and subclinical disease in its different forms? Of development and maintenance of carrier status? What risks do vaccines present (e.g., contamination with virulent strains, creation of carriers, confounding of diagnostic tests)? What is the interaction between vaccination and diagnostic tests? At the national level, what are the trade implications? What authorization is required to use them? If use is forbidden, what is the rationale?

• If economic decisions are involved, what are the relative costs of the infection in groups and the costs of prevention and control measures?

For some diseases, the most of the answers to the above questions are well established. For many, they are not and you will have to reason by analogy from other diseases and species where the answers are clearer. The goal of this module is to acquaint you with the underlying epidemiologic concepts that are useful in considering the above questions when working with disease problems occurring in animal groups (e.g., kennels, hospital wards, livestock herds, stables, fairs).

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The Epidemiologic Triangle (Triad):

Disease is the result of complex interactions (some would say imbalance) between the triad of the agent (toxic or infectious), the host and the environment. The components of this interaction differ depending upon the specific circumstances of each group of affected animals. Particularly for agricultural animals, this triad is strongly influenced by husbandry and management factors, which are often the most important. For vector-borne diseases, vector factors are also linked to the other factors.

Recognizing the different components of this triad is important because they are the source of opportunities to reduce disease at multiple points in the transmission cycle. A common mistake is to focus on only one aspect of the triad for disease control or prevention and to overlook the others.

 

Agent Factor Examples:

Dose
Environmental hardiness
Virulence (microbial)
Infectivity (microbial)
Toxicity (poisons)

Host Factor Examples:

Innate resistance (e.g. gastric barrier, mucocilliary transport mechanism)
Previous exposure
Passive immune status (neonates)
Vaccination status and response
Age
Gender
Behavior (e.g. mutual grooming, dominance, pica)
Production status (e.g., lactating vs. non-lactating)
Reproductive status (e.g., pregnant vs. non-pregnant, sterile vs. intact)
Genetics

Intrinsic (non-changeable in the individual):

Age is very important because the risk of many diseases change widely over the animals life time due to underlying physiological changes that are associated with age. Neonates are very susceptible to many enteric and respiratory infections but resistance increases as the animals mature. As immune function declines with advanced age, susceptibility begins increasing again.

Clinical disease due to ubiquitous agents, such as the viral scour agents, can be reduced by delaying the neonate's exposure to the agent (innate resistance increases with age) and reducing the infectious dose by changing the environmental factors.

Due to genetics different breeds have different risks for diseases, such as hip dysplasia in German Shepherds. Within breeds, some infectious diseases occur due to underlying genetic defects (e.g., Holstein BLAD, Arab CID, Quarter Horse HPP).

Extrinsic (changeable in the individual):

Intact bitches are at risk of pyometra and mammary gland tumors than spayed (excluding stump pyometras) are not. Intact dogs behave differently than non-intact dogs, tending to roam more and thus being at higher risk of being hit by cars and of acquiring communicable infectious diseases.

Vaccination increases an individual’s resistance to disease but the protection is not absolute for most biologics.

Environmental Factor Examples:

Animal stocking density
Animal movement between groups
Housing (e.g. ventilation, sanitation)
Environmental conditions (e.g. temperature, humidity, wind velocity, precipitation)
Nutrition (protein, energy and macromineral and micromineral adequacy)

Many infectious agents are susceptible to the ultraviolet (UV) in direct sunlight and to desiccation. Many infectious agents survive for long periods in damp environments.

Strangles (Strep. equi) in horses appears to occur more frequently during damp cold weather. This is likely because the agent is able to survive longer in damp environments.

Salmonellosis in all animals including humans occurs more frequently during summer than during other times of the year. This is likely because the agent is able to replicate to infectious doses in moist feedstuffs at summer temperatures.

Bluetongue virus grows more rapidly in Cuilicoides variipennis at higher temperatures. Mullens BA et al. (1995). Med Vet Entomol 9:71-76.

A strong association has been shown between bluetongue infection in cattle and both temperature and rainfall. Ward MP (1996). Vet Res Commun 20:273-283.

These factors interact in complex ways that are often under the control of man.

EX: Increased animal density may lead to increased microbial load in the environment, a roof may prevent exposure of microbe to killing UV, low ventilation may increase humidity from animal respiration which in turn increases environmental survival of the organism which in turn increases exposure dose and infects more animals.

It has been said that:

"Bovine mastitis is a disease of man with signs in the cow."

"Bad management will overwhelm the best immunology."

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The Spectrum of Disease Severity (Gradient of Infection):

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Transmission of most communicable infectious agents will not continue within an exposed group of animals if the proportion of resistant animals in that group is above a threshold level, typically 70 to 80%. This level depends upon the agent and factors influencing the likelihood of transmission, such as animal density and the typical dose of the agent. This resistance can be passive immunity (acquired antibodies), active immunity (previous infection or immunization) or innate resistance.

On the other hand, if the animal density or the agent dose is significantly high, all individuals in a population may effectively be susceptible to infection even with adequate vaccination.

Examples:

Based on evidence showing that outbreaks of rabies in dogs will not propagate if between 39% and 57% of dogs in an area are vaccinated, WHO recommends immunizing at least 70% of the dogs in a population. Vaccine (1996) 14:185-186.

Even though evidence shows that Brucella vaccination protects only approximately 60% of vaccinated animals from infection, evidence also shows that an outbreak of Brucella abortion will not propagate in a fully vaccinated herd.

For herd immunity to stop an outbreak of human measles, it is estimated 94% of the population must be immune. In human population centers of over 500,000 people, measles will cycle continually without vaccination because of the continually emerging pool of susceptibles.

Caution: A common error is to assume that because a vaccine or bacterin is approved by the USDA and is marketed, it is efficacious. For a surprising number of veterinary vaccines, evidence of efficacy is either lacking (which means that it may or may not be efficacious) or the evidence suggests that the vaccine is not efficacious. Many veterinarians and producers don't realize that evidence of field efficacy is not required as part of the USDA vaccine licensing process and subsequent evidence of lack of field efficacy does not jeopardize a license.

For example, current bacterins against host-adapted organisms causing chronic infections, such as leptospira, have been found to lack efficacy. See Bolin CA et al. Am J Vet Res 50:2004-2008 (1989), Am J Vet Res 52:1639-1643, (1991).

For a review of the field evaluation of respiratory vaccines (or its absence), see Perino, LJ, BD Hunsaker (1997). A review of bovine respiratory disease vaccine field efficacy. Bov Pract 31(1):59-66.

For further information on the USDA approval process and its lack of requirements for evidence of field efficacy, see Meyers, LL (1983). Federal regulation of the efficacy of vaccines used in cattle in the United States - A need for change. Pp. 299-302 in: Proc 4^th Int Symposium Neonatal Diarrhea, Univ Saskatchewan, 1983.

Cited in: Radostits, OM (1991). The control of infectious diseases of the respiratory and digestive tracts of cattle. Can Vet J 32:85-89.

For the current status of small animal vaccines, see Pedersen, NC (1997). Perspectives on small animal vaccination: A critical look at current vaccines and vaccine strategies in the United States. Pp. 145-156 in: Scientific Presentations of the 64^th Annual Meeting Amer Animal Hospital Assoc, March 8-12, 1997, San Diego, CA. ISBN 0-941451-59-3.

R₀ ("R Zero"): The average number of susceptible animals that are infected by each infected animal. This is a measure of the ease of transmission of an infectious agent.

EX: For epidemics of airborne viral diseases such as Foot-and-Mouth disease in susceptible populations, the reproductive ratio is on the order of 70. This is due to the production of viral aerosols, particularly by swine, that can travel for long distances and in part accounts for the drastic measures taken against this disease.

EX: For a disease such as IBR in a dairy herd, the reproductive ratio is around 7. Rijsewijk & Wentink Vet Micro 53:169-180 (1996).

For communicable infections to progress, on average each infected animal must infect one or more susceptible animals. If each infects more than one, the outbreak increases exponentially. If on average each infects less than one, the outbreak decreases. If on average each infects one, in large populations the outbreak progresses at a constant rate.

Over the long run, an R₀ equal to or greater than one is required for an infectious agent to survive in a group. If it can be lowered to less than one (the veterinarian's objective), eventually the agent will be eradicated from the group. The goal of control and prevention strategies for infectious disease is to reduce R₀ below one if not to zero.

Reducing R₀ can be done at any point in the transmission cycle by:

• Reducing or eliminating the shedding of the agent by the infected host.

EX: Treating or removing the infected host. However, detecting these infected hosts is not always straightforward, particularly if they have always been subclinical. Chronic subclinical carriers of leptospira can be treated with long-acting antibiotics. Cattle persistently infected with BVD can be detected by laboratory testing and removed from the herd.

• Reducing the duration of environmental survival of the agent

EX: Sanitation (carrying out effective sanitation isn't as straightforward as it first appears), exposing the agent to sunlight, drying the environment.

• Reducing or eliminating vehicle contamination and fomite transmission

EX: Preventing contamination of feedstuffs and water and adequate sanitation of items that come in contact with the animal's mouth or other portal of entry.

In general, we need to practice better "food safety" for all animal feedstuffs because many of them will support replication of food-borne pathogens when moist and warm. Fomites such as livestock trailers are often overlooked for diseases such digital dermatitis ("hairy foot wart") in cattle.

• For vector-borne infections reducing the vector population or preventing exposure of susceptible animals to it.

EX: Applying pesticides, removing animals from vector inhabited areas.

Many vectors such as flies develop resistance to pesticides fairly quickly. Pesticides also affect many other beneficial insects, which often are more sensitive than the target species. For more effective long term reductions of vector populations, attack their life cycles at multiple points rather than attacking a single point as is commonly done.

• Reducing the exposure of susceptible hosts.

EX: Decreasing animal stocking density for agents transmitted by contact, increasing ventilation of enclosed housing for airborne agents, preventing contamination of vehicles such as feed and water, isolation of infected animals during clinical illness and the carrier state, maintaining youngstock groups that are more uniform in age.

Accomplishing this exposure reduction often requires management and housing changes that owners may not be willing or able to make. For example, an "all in, all out" policy is a very effective means of reducing transmission but it usually requires major changes in facilities and management practices to accomplish it.

• Increasing the resistance of the susceptible hosts.

EX: Prior vaccination with an efficacious vaccine, maximizing transfer of maternal antibodies, adequate balanced nutrition (particularly of the trace elements and vitamins involved in immune system function).

Modern animal husbandry and the associated environmental modification often dramatically increase the R₀ for infectious agents that co-evolved and survived successfully with their hosts under entirely different environments. For example, we house animals in enclosed airspaces, which unless managed carefully can markedly enhance the transmission of aerosol-born agents. We group animals together much more densely than they are in nature, which increases the level of environmental contamination and markedly increases the opportunity for contact between infected and susceptible animals. We also manage the animal's environment in ways that enhances the survival of infectious agents, such as providing roofs that protects infectious agents from the UV in sunlight or recycling fecal-contaminated water that transports water-borne infectious agents back to susceptible animals.

EX: Consider the medical ecology of Fasciola hepatica in the native grazing environment (scarce water, infrequent flooding of forage, low density of animals) compared to irrigated pastures (regular source of water, high density of animals).

EX: A dramatic example of the effect of increasing R₀ through animal husbandry is the association between the concentration of wildlife, such as birds and cervids (elk, deer), at winter feeding stations and the associated infectious disease outbreaks.

In the past, too much emphasis has been placed on using vaccination as the sole means to control and prevent disease outbreaks and not enough on the many other factors under management control, such as animal housing design, animal contact control and basic sanitation practices. Basically, not enough emphasis has been placed on good animal husbandry.

Attacking the transmission cycle of a disease or the causal chain of a disease at several critical control points will enhance the biosecurity of a group of animals. Then, if intervention at one point fails, control will still be maintained by the interventions at the other points.

Although most vaccines reduce the number of clinical cases and the number of infections that would have occurred in a group during an outbreak, this prevention is not absolute. Most vaccines do not prevent all infections. Rather, in a group of animals most vaccines at best will reduce the number of animals infected, will reduce the proportion of those that become clinical cases among those that are infected and will reduce the amount and duration of shedding in those that are infected. But, as noted above, some vaccines don't even do this much.

EX: Strep. equi bacterins are estimated to reduce the number of clinical cases by approximately 50%.

Plots of the number or proportion of animals affected in a group over time.

Epidemic curves are useful to determine what type of exposure occurred and what type of transmission is occurring in a disease outbreak. In turn, this information is useful to help determine what likely caused the outbreak and what interventions will likely stop it.

Point Source Epidemics: Point source epidemics occur when an index case or a "vehicle", such as contaminated feed, exposes most of the susceptible animals in a group at once. In the case of an infectious agent, this exposure was by a dose sufficient high to cause clinical disease in most exposed animals and if the exposure is to an index case the R₀ was initially very high. Thus, most cases occurred within the typical range of the incubation period and no further transmission occurred.

Propagating Epidemics: Propagating epidemics occur when infected animals transmit the infection to susceptible animals over time. Exposure of susceptibles occurs over time rather than all at once as above. These epidemics progress through a group over a period of time that is considerably longer than the typical incubation period.

Most likely a change in some host, agent or environment factor markedly increases the R₀ and infections that would have been subclinical and unrecognized now become clinical and recognized. Because clinical cases usually shed much more of the infectious agent than do subclinically infected animals, the level of environmental contamination increases, increasing the infectious dose to other individuals in the group. More of these now begin having clinical rather than subclinical infections and the outbreak grows.

A causal web is the linkages between a set of agent, environment and host factors that have been shown to result in disease. Disease usually develops because of a chain of causes, rather than a single cause, that have acted one after another or together, often in complex ways. The purpose of developing a causal web is to provide "the big picture"; a framework for thinking about the relationships between these causes and for developing strategies for controlling and preventing the condition in a group of animals. The relative importance of each component depends on the actual factors involved in the specific situation. Part of the detective work of solving disease problems in groups is determining which factors are most important in a particular situation and which of these are the easiest to change.

The following are two examples of causal webs modified from the bovine respiratory disease section of the Large Animal Medicine Notes "Epidemiology of Pneumonia in Feedlot Cattle" (S. Wikse).

Note that although the basic pathophysiological mechanism is similar in both, the critical control points are considerably different between older cattle housed outdoors in open feedlot pens and neonatal calves housed in enclosed barns. Note also that the relationships between the selected factors are fairly complex.

Causal Web (Path Model) of Risk Factors of Housed Calf Bronchopneumonia

Causal Web (Path Model) of Risk Factors of Feedlot Calf Bronchopneumonia

Infection occurs in an animal when the infectious dose exceeds its resistance, innate or acquired, against that infection. For many of the ubiquitous infectious agents, infection occurs at some point in almost every animal's life. Providing that the animal has sufficient resistance, most of these infections are subclinical and the animal develops immunity. However, if the dose received by the animal is sufficiently high, it will develop a clinical case rather than a subclinical infection. Outbreaks of clinical disease occur when more susceptible hosts than normal are infected with infectious doses that are sufficient to cause clinical disease.

For many infectious agents, clinical cases shed the infectious agent at higher levels for longer time than do subclinical cases. Thus, the infectious dose often increases as more animals develop clinical cases rather than subclinical cases and the environment becomes more heavily contaminated as a consequence. In turn, more infections occur in animals that were resistant to the lower infectious dose and more clinical cases develop. Until the transmission of the infectious agent is reduced, the infectious dose lowered, the resistance of the remaining unaffected animals is increased or the pool of susceptibles is exhausted the outbreak expands in a vicious spiral.

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Anderson, RM, RM May (1982). Population Biology of Infectious Diseases. Springer-Verlag.

Anderson and May wrote this book and a number of other papers on the theory of the transmission of infectious agents, herd immunity and vaccination. Searching on either of their names will identify those papers.

Chapter 17: Medical Ecology in: Schwabe, CW (1985). Veterinary Medicine and Human Health, 3^rd ed. Williams and Wilkins. ISBN 0-683-07594-2.

Numerous examples of the causal webs for different types of diseases.

Ewald, PW (1996). Evolution of Infectious Disease, Oxford Univ Press; ISBN: 0195111397

Mims, C, N Dimmock, A Nash, J Stephen (1995). Mims' Pathogenesis of Infectious Disease, 4^th ed. Academic Press. ISBN 0-12-498263-8 pprbk.

General description of the natural history of infectious disease processes, emphasizing the interaction between host and agent factors.

Relevant On-Line Materials:

Ewald, PW (1996).Guarding Against the Most Dangerous Emerging Pathogens: Insights from Evolutionary Biology. Emerg Infect Dis 2:245-256.
http://www.cdc.gov/ncidod/eid/vol2no4/ewald.htm

Lederberg, J (1997). Infectious Disease as an Evolutionary Paradigm. Emerg Infect Dis 3:417-423.
http://www.cdc.gov/ncidod/EID/vol3no4/lederber.htm

Nesse, RM, GC Williams (1998). Evolution and the Origins of Disease. Sci Amer
http://www.sciam.com/1998/1198issue/1198nesse.html

Benenson, AS (1995). Control of Communicable Diseases in Man, 16^th ed. American Public Health Association, ISBN: 0875532225.

Last, JM (1995). A Dictionary of Epidemiology, 3^rd ed. Oxford University Press, ISBN 0-19-509668-1. 180 pp., pprbk.